A DNA chip generally includes a carrier usually of planar design, on which a microarray of spots is arranged. A spot contains catcher molecules, for example oligonucleotides, immobilized on the surfaces of carrier and electrodes.
In order to carry out an analysis, an analyte solution containing target molecules, for example DNA fragments, is applied to the spots. In the case of a complementary matching in the base sequence, the target molecules couple to the catcher molecules of a spot. The reading-out of the analysis result, that is to say the determination of those spots in which coupling or binding events have taken place, may be effected optically, calorimetrically or electrically, by way of example.
DE 196 10 115 C2 and the publication “Nanoscaled interdigitated electrode arrays for biochemical sensors”, Van Gerwen et al., Sensors and Actuators, B49, 1998, 73-80, Elsevier Science S. A., disclose electrically readable DNA chips having two-pole microelectrode systems for the electrical detection of binding events. These systems are each formed from a pair of comblike, intermeshed electrodes to which AC current is applied. Binding events that take place in the region of the electrodes alter electrical parameters such as e.g. the conductance and the specific capacitance of the analyte and can accordingly be detected with the aid of the microelectrode system.
What is problematic in the case of DNA chips of this type is that the dimensioning of the electrodes is very large in comparison with the molecular dimensions of the catcher molecules present in a monomolecular layer on the carrier and electrode surface. Binding events that take place there can therefore be detected only with difficulty. Van Gerwen et al. propose miniaturizing the electrodes in order to improve the measuring effect or the sensitivity. However, limits are imposed on miniaturization for technical and economic reasons.
A further problem resides in the fact that relatively high electrolyte conductances and accordingly low analyte resistances are present during the detection of biochemical molecules. They have superposed on them the usually very high electrode impedance brought about by the electrolyte double layer capacitance between electrodes and analyte. It is virtually impossible to separate analyte resistance and electrode impedance. Moreover, very high measurement frequencies are necessary on account of the small analyte resistance. This is very difficult with conventional measurement technology, however, since parasitic capacitances such as cable capacitances, etc. disturb the measurement.
In the case of conventional DNA chips, therefore, the measuring effects for determining the capacitance or the resistance of the analyte are very weakly pronounced or absent. What is more, the measurement frequencies have to lie in the MHz range. Moreover, all chemical or physical processes that take place at the electrodes influence the measurement between the electrodes, thus e.g. coatings with biochemical molecules, polarizations, corrosion of the electrodes, film formation, etc.
Furthermore, DE 100 15 816 A1 discloses an electrically readable DNA chip which enables a two-pole electrode system for the electrical monitoring of a redox cycling process. If appropriate, in this respect there may furthermore be a third electrode with potential application for the control of the redox cycling process.